title: Wnt/β-catenin signaling regulates MAPK and Akt1 expression and growth of hepatocellular carcinoma cells.
abstract: In hepatocellular carcinoma (HCC), Wnt/β-catenin, Ras/MAPK and PI3K/AKT signaling pathways form a complex network and play important roles during HCC genesis and development. To study their relationship and the influence on cell growth, the siRNA directed against β-catenin was transfected into HCC HepG2 cells. β-catenin mRNA and protein levels were measured respectively at various times by RT-PCR and Western blot. Furthermore, HCC cell growth was measured by MTT assay. Finally, MAPK family and Akt1 protein levels were also measured by Western blot. After the transfection, β-catenin mRNA levels were markedly inhibited at 24 h and increased gradually at 48, 72 and 96 h; β-catenin protein levels decreased gradually at 24, 48 and 72 h and slightly increased at 96 h. HCC cell growth was inhibited from 24-72 h, but this inhibition decreased at 96 h. ERK1/2 (p42/p44 MAPK), JNK/SAPK, p38 MAPK, and Akt1 protein levels showed no change following transfection, while their phosphorylated protein levels showed changes. Thus, siRNA directed against β-catenin markedly decreased β-catenin gene expression and inhibited cell growth. Wnt/β-catenin signaling pathway might regulate Ras/MAPK and PI3K/Akt signaling pathways through regulation of the phosphorylation state of ERK1/2, JNK/SAPK and Akt1 protein in HCC HepG2 cells. These pathways might compensate for the inhibitory effect of β-catenin, thereby affecting tumor cell growth and others downstream factors.
authors.affiliation: Department of Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin Province, China.
authors.forename: X H
authors.initials: XH
authors.lastname: Wang
authors.forename: X W
authors.initials: XW
authors.lastname: Meng
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.forename: B R
authors.initials: BR
authors.lastname: Liu
authors.forename: M Z
authors.initials: MZ
authors.lastname: Han
authors.forename: Y J
authors.initials: YJ
authors.lastname: DU
authors.forename: Y Y
authors.initials: YY
authors.lastname: Song
authors.forename: W
authors.initials: W
authors.lastname: Xu
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: C495270:CTNNB1 protein, human; D051153:Wnt Proteins; D051176:beta Catenin; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases